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[Study of the inhibition produced by adriamycin against specific enzymes in the rat heart].

Adriamycin is used for the treatment of leukemia and other neoplastic processes. Unfortunately the drug has a toxic effect on some tissues. Cardiotoxicity in particular limits the use of the drug. Several hypotheses have been given to explain adriamycin heart toxicity. The authors have studied the effect of the drug on the enzymes isocitrate dehydrogenase-NADP, malic enzyme, 6-P-gluconate dehydrogenase, malic dehydrogenase-NAD+, hexokinase, and phosphofructokinase. They observed that adriamycin inhibits the NADP-dependent enzymes, and that the sulfhydryl group of the enzymes may be involved in the inhibitory action of adriamycin.

Animals↗

Solitary adult xanthogranuloma: a case report with new observation on lipid droplet formation.

A case of solitary xanthogranuloma was studied by optical and electron microscopy. The tumor parenchyma cells were composed mainly of multilocular lipid droplets together with rough-surfaced endoplasmic reticulum, a few mitochondria, glycogen particles, and fine filaments sparsely scattered throughout the cytoplasm. The parenchyma cells bore a close structural resemblance to Ito's "fat-storing cells" which are situated in Disse's space, contain lipid droplets and are thought to be the only cells participating in intralobular fibrillogenesis in the liver. Another notable finding was that the lipid droplets of the tumor parenchyma cells originated directly from rough-surfaced endoplasmic reticulum. Thus, the tumor morphology was incompatible with the currently favored concept of a benign, reactive non-neoplastic process of prominently histiocyte cells, being characterized instead by prominently fibroblastic cells.

Adult↗

[Lymphatic manifestation forms in the terminal phase of chronic myelocytic leukemia].

A blastic transformation in chronic myeloic leukaemia (CML) is reported, which, on the one hand, is characterized by the "lymphoid" feature of blasts and, on the other hand, by the appearance of great lymph node swellings. The clear distinction from (secondary) malignant lymphomas may be difficult. The inclusion of such forms of blastic transformation in CML is based on cytogenetic findings. Their non-granulocytic or "lymphoid" nature emerges from their cytological behavior. The fact that these lymphoid transformations respond to vincristin and prednison emphasize that their recognition as special entities is justified. They also demonstrate that the neoplastic process in CML may not only involve myelopoietic but pluripotent stem cells as well.

Adult↗

A general concept for molecular biology of cancer.

The demonstrations that "fetal" isozymes and other fetal or "oncodevelopmental" antigens are present in tumor cells has led to the general concept that genes normally silent in adult tissues are activated during the neoplastic process. Recent evidence that some chromatin proteins of tumor cells are fetal antigens has suggested that some of the "switches" involved in gene activation for tumor growth may also be fetal or oncodevelopmental. These results have led to current theoretical concept that fetal gene derepressors interact with the genome to produce messenger RNA for the protein products involved for growth, invasiveness, and metastasis. These processes may not be controllable in adult cells because of the lack of inhibitors, which were present during embryonic development but are not produced in adult tissues.

Animals↗

A comparative study of the pancreatogram and the histological findings in 2,2'-dihydroxy-di-N-propylnitrosamine-induced pancreatic carcinoma in golden hamsters.

2,2'-dihydroxy-di-N-propylnitrosamine (DHPN) at a dose of 250 mg/kg was injected subcutaneously into 28 male Syrian golden hamsters once a week. They were sacrificed and dissected at intervals of one to two weeks beginning from the 8th week until the 20th week after the injection. Pancreatography was performed on every hamster and the chronological changes in their pancreatograms were compared with the histological findings. Marked atypical hyperplasia almost indistinguishable from carcinoma in situ was observed histologically beginning at the 13th week, and infiltrating adenocarcinoma was seen in all the hamsters in and after the 16th week. The pancreatography made it possible to depict even minute changes at an early stage that corresponded to the histological findings. One example was that a slight stenosis in the branch was detected at the 13th week and the picture of stenosis was observed in the main pancreatic duct at the 14th-15th week. This was followed by obstruction in and after the 16th week. These findings support the possibility that the neoplastic process in the hamster pancreas occurs in the branch region earlier than in the main pancreatic duct.

Amylases↗

Report on the United States experience with cimetidine in Zollinger-Ellision syndrome and other hypersecretory states.

Sixty-one cases of the Zollinger-Ellison syndrome, encountered over a 2-year period, have been treated with cimetidine, half of them for over 1 year. Two-thirds of the patients responded to 300 mg of the drug every 6 hr by mouth. Others required up to 600 mg every 6 hr. In adequate doses the drug was highly effective: it controlled pain and dyspepsia, restored weight, abolished diarrhea, and allowed healing of ulcers and other inflammatory conditions. Missed or reduced doses led to rapid return of symptoms. Progression of the basic neoplastic process, with associated secretory drive, was unimpeded. Patient acceptance of the drug was 100 percent, and apart from minor transient abnormalities, gynecomastia (5 cases) and liver dysfunction (3 cases), which resolved while treatment continued, no serious adverse effects were seen. Of 61 patients 48 are still on the drug, 3 who were well controlled were treated surgically, 5 died for reasons unrelated to therapy, and 5 had significant problems. The drug provides an alternative to total gastrectomy and can be recommended with confidence for the suitably selected patients. The drug was also beneficial in some cases of the short bowel syndrome, systemic mastocytosis, and endogenous hyperhistaminemia due to leukemia.

Adult↗

[Diffuse malignant lymphoma with small cleaved cells preceded by erythroderma with non-caseous granulomatous infiltration of the skin and leukemoid reaction].

This is a description of a case in a man who developed non-Hodgkin lymphoma of small cleaved cells preceded by erythroderma with leukemoid reaction. Non- caseous granulomas with Langhans' cells were found in the skin biopsy. The etiologic agent was not identified until the neoplasia that killed him was demonstrated. Autopsy study showed lymphomatous infiltration in all ganglionaries groups, the skin, lungs, kidney, liver, spleen, adrenal glands and bone marrow. One of the interesting aspects of the case in the tissue reaction to the neoplastic process, a fact already described but rarely observed.

Adult↗

[Association of primary malignant neoplasms in the same patient].

The Authors have examined the problem concerning the presence of "Double malignancies" in the same patient, on the basis of a review of the literature and of an investigation of their own case material (nine patients: six with double solid tumours and three with a solid tumour and an associated haematologic neoplasia). The Authors discuss the time sequence of the two neoplastic processes and the immunological pattern (T and B lymphocytes) of all cases.

Adenocarcinoma↗

[Clinical morphological characteristics of dimorphic lung cancer].

Twenty three cases of dimorphous lung cancer are analysed. There were found some specific features of the clinico-morphological picture of the neoplastic process in question: slow development, a predominant peripheral tumor growth, large size tumors, less pronounced local invasion of dimorphous cancer, comparatively rare metastases (34.8%). Three variants were distinguished in the combination of squamous cell and glandular foci: adenoepidermoid, squamous cell and mucoepidermoid ones.

Adenocarcinoma↗

[Malignancy of hormonally active ovarian tumors].

401 cases of hormone-producing tumors of the ovary were studied (190 theca-cell, 169--granulose cell, 25--mixed thecagranulosa cell and 17--virilising tumors). Histological diagnosis, clinical stage and end results of their treatment were compared. Theca-granulosa cell tumor is considered to be the most malignant form of these neoplasms. Pure theca-cell tumor proved to be benign in most cases. Of special interest is a high percentage of patients being cured at stage 1 (FIGO classification) of neoplastic process, that stands, in the authors' opinion, in close relationship with comparatively good results obtained in these patients.

Adenoma↗

Lipid bodies: cytoplasmic organelles important to arachidonate metabolism in macrophages and mast cells.

Much has been learned about the biochemical nature and pharmacologic activity of the products of arachidonic acid (AA) oxidation, but relatively little is known about the structures in nucleated cells into which AA is incorporated and from which it is initially mobilized. To address this question, we administered 3H-AA or other 3H-fatty acids in vitro to human lung mast cells and alveolar macrophages as well as to mouse and guinea pig peritoneal macrophages. The subcellular distribution of 3H label was assessed by electron microscopic autoradiography, and the nature of cell-associated 3H-lipids was determined by thin layer chromatography. Autoradiographic analysis of human lung mast cells localized virtually all of the 3H-AA to cytoplasmic lipid bodies. Lipid bodies are roughly spherical, variable osmiophilic, nonmembrane-bound structures that appear in the cytoplasm of a wide variety of cells, but we have found that these lipid bodies occur with increased frequency in granulocytes, macrophages, and mast cells at sites of inflammatory, immunologic, or neoplastic processes. Macrophages also incorporated 3H-AA predominantly into cytoplasmic lipid bodies. In contrast to mast cells, however, macrophages incorporated 3H-AA into the plasma membrane as well. Stimulation of macrophage phagocytosis resulted in striking alterations of the relationships of lipid bodies to intracellular membranes, so that many lipid bodies appeared adjacent to phagolysosomes. In addition, some phagolysosomes contained 3H label, which along with other morphologic evidence suggested that lipid bodies may discharge their contents into these structures. Mast cell and macrophage cytoplasmic lipid bodies appear to represent a major site of intracellular storage and metabolism of products of AA and perhaps other fatty acids taken up from the external milieu. These heretofore neglected organelles may thus influence cellular function in a wide variety of adaptive or pathologic processes.

Animals↗

Pigmented villonodular synovitis (giant-cell tumor of the tendon sheath and synovial membrane). A review of eighty-one cases.

We reviewed the cases of eighty-one patients with pigmented villonodular synovitis and giant-cell tumor of the tendon sheath. The average duration of symptoms prior to consulting a physician was twenty-seven months. The lesion was slow-growing, was located in one joint or tendon sheath, and usually was asymptomatic in a finger or thumb but painful in a knee or toe. Twenty-nine per cent of the finger or thumb lesions and 21 per cent of the knee lesions that were followed recurred. Approximately 70 per cent of the radiographs showed abnormalities that ranged from soft-tissue swelling to bone erosion. Six lesions were incidental findings during arthrotomy for some other lesion. The histological characteristics of the solitary nodular, multiple nodular, and diffuse lesions suggested that they have a common histogenesis that is characterized by proliferation of fibroblastic or histiocytic mesenchymal cells, or both, beneath the synovial or tenosynovial lining cells, and by collagen production. Foam cells and iron deposits appear to be secondary changes and are usually seen in the periphery of the expanding nodules. The centrifugal growth pattern and the distinct differences between the lesional tissue and the adjacent hyperplastic synovial tissue suggest that pigmented villonodular synovitis is a true neoplastic process.

Adolescent↗

Cellular adenomyoepithelioma of the breast.

This report is the second documented case of an adenomyoepithelioma arising in the breast. The neoplasm was well circumscribed and possessed cytologic features suggestive of a low-grade cancer; however, its biologic behavior remains undefined. The epithelial and myoepithelial elements are characterized ultrastructurally, and both are active participants in the neoplastic process. There are some histologic similarities of this lesion to the salivary gland epithelial-myoepithelial carcinoma; however, the growth pattern of cellular interductal proliferation of myoepithelium is unique.

Breast Neoplasms↗

[Leukocyte migration inhibition reaction in melanoma].

Under study was the reaction of suppression of leucocytes migration in 28 patients with melanoma and in 15 healthy donors. In patients with the local neoplastic process the suppression of their lymphocytes migration under the melanoma extract influence was much more frequently observed and wos more significantly pronounced than in healthy donors and patients with metastases, especially in cases of wide tumor spread. Enhanced migration noted in a number of cases was associated with an unfavourable clinical course. Likewise, the enhanced migration was observed 2--3 weeks following resection of primary melanoma and in one case--at the end of the chemotherapy course.

Cell Migration Inhibition↗

Retinoid feeding, hormone inhibition, and/or immune stimulation and the genesis of carcinogen-induced rat mammary carcinomas.

Female Sprague-Dawley rats were treated at 53 days of age with a single intubation of 7,12-dimethylbenzanthracene (DMBA). Three days after carcinogen treatment, the animals were treated with retinyl acetate (RA) (at 3 dietary levels), hormone inhibition (HI) [tamoxifen (1-rho-beta-dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene) plus 2 bromo-alpha-ergocryptine], and/or immune stimulation (methanol-extracted residue of Bacillus Calmette-Guérin, cell wall skeleton of Nocardia rubra, or cell particulate of DMBA-induced rat mammary carcinomas plus Freund's complete adjuvant). RA at 0.6 or 1.0 mM concentrations per kg diet significantly reduced the incidence of mammary carcinomas; 0.2 mM concentrations of RA per kg diet did not affect tumor incidence. HI also significantly decreased mammary carcinoma incidence, an effect which was significantly enhanced by all 3 dietary levels of RA. Immune stimulation by methanol-extracted residue of Bacillus Calmette-Guérin or cell wall skeleton of Nocardia rubra did not affect mammary carcinoma incidence when administered either alone or in combination with RA and/or HI. The cell particulate of DMBA-induced rat mammary carcinomas plus Freund's complete adjuvant significantly reduced mammary carcinoma incidence in rats fed RA but did not affect mammary carcinoma incidence in placebo-fed rats or in rats treated only with HI. However, in rats treated with the triple combination of cell particulate of DMBA-induced rat mammary carcinomas plus Freund's complete adjuvant, RA, and HI, no mammary carcinomas were observed for the duration of treatment (20 weeks after DMBA administration). Although HI was always superior to RA feeding in the prophylaxis of this neoplastic process, a significant synergism between these two treatments was consistently observed. This distinct synergism was observed even when using the low dietary level of RA, an amount of RA which by itself was ineffective in the suppression of mammary carcinogenesis. With but one exception, immune stimulation did not significantly influence this carcinogenic process, either when administered alone or when administered to rats with a reduced mammary carcinoma burden, i.e., animals treated with RA and/or HI.

9,10-Dimethyl-1,2-benzanthracene↗

[Morphological studies of cultured cells derived from human cervix with normal and abnormal epithelium].

Primary explant tissue cultured cells and their subcultured cells were studied morphologically as basic research into the neoplastic process in the uterine cervix, or into the cellular difference between carcinoma in situ (cis) and invasive carcinoma. We cultured cells derived from normal squamous epithelium, dysplasia, cis and invasive carcinoma, and these cultured cells were observed by light and electron microscopy. The following results were obtained: A cultured medium with D-valine substituted for L-valine was used, and it was found that the medium clearly inhibited the outgrowth of fibroblasts, but did not inhibit the outgrowth of the epithelial cells. The cultured cells from the normal, dysplasia and cis could be passaged three times. These cultured cells derived from the normal and each abnormal epithelium had different growth patterns. In addition, the morphological features of these cultured cells resembled those of each in vivo. There was no difference in the findings for the subcultured cells.

Cell Division↗

Modifying factors in pancreatic carcinogenesis in the hamster model. I. Effect of protein-free diet fed during the early stages of carcinogenesis.

The role of protein in pancreatic carcinogenesis was examined in outbred Syrian golden hamsters treated with the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine (BOP) and fed a purified protein-free diet (PPFD). The PPFD was fed for 28 days from 8 weeks of age; before and after animals were fed PPFD, they were given a commercial diet (CD). BOP was given before PPFD feeding (group 1) or at 18 days (group 2) and 28 days (group 3) from the beginning of the PPFD feeding. BOP-treated control hamsters (group 4) were pair-fed a purified control diet (PCD) instead of PPFD. All animals fed PPFD and PCD were returned to a CD for the rest of the experiment, which was terminated in each group 52 weeks after BOP treatment. The results showed a highly significant reduction of tumor incidence (P less than 0.0001) in hamsters that received PPFD, when compared to those fed PCD, regardless of the time of carcinogen administration during the dietary regimen. Hamsters treated with BOP at 18 days of PPFD (group 2) developed neither benign nor malignant pancreatic tumors. The inhibition of pancreatic neoplasms was not related to reduced calorie consumption, since this occurred in the BOP-treated hamsters that were pair-fed the PCD diet. The results indicated that both the initiation and promotion of pancreatic carcinogenesis with BOP in hamsters can be inhibited by lack of protein in the diet given for 4 weeks during the early stages of the neoplastic process.

Animals↗

[Conservation of the mandible by osteotomy-osteosynthesis in "trans-mandibular" oropharyngectomy. 34 case reports].

Trans-mandibular oropharyngectomy was performed in 34 patients, as initial treatment in 20 cases and following tumoral recurrence after radiotherapy in the other 14 cases. Results indicate that mandibular conservation is possible when bone is not affected by the neoplastic process and when an oropharyngoplasty ensures perfect covering of the mandible. The site of choice for osteotomy-osteosynthesis appears to be the parasymphysial region, as this provides a very satisfactory route of approach, the mental nerve and innervation of the lip are respected, it is situated outside of the irradiation field (before or after surgery), and there are no dental articulation complications.

Humans↗